PODXL_RAT
ID PODXL_RAT Reviewed; 485 AA.
AC Q9WTQ2; Q6IRK7; Q9R068;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Podocalyxin;
DE AltName: Full=Podocalyxin-like protein 1;
DE Short=PC;
DE Short=PCLP-1;
DE Flags: Precursor;
GN Name=Podxl; Synonyms=Pclp1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kobayashi T.;
RT "Rat podocalyxin.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=10982412; DOI=10.1091/mbc.11.9.3219;
RA Takeda T., Go W.Y., Orlando R.A., Farquhar M.G.;
RT "Expression of podocalyxin inhibits cell-cell adhesion and modifies
RT junctional properties in Madin-Darby canine kidney cells.";
RL Mol. Biol. Cell 11:3219-3232(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH EZR; SLC9A3R1 AND SLC9A3R2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11457882; DOI=10.1172/jci12539;
RA Takeda T., McQuistan T., Orlando R.A., Farquhar M.G.;
RT "Loss of glomerular foot processes is associated with uncoupling of
RT podocalyxin from the actin cytoskeleton.";
RL J. Clin. Invest. 108:289-301(2001).
CC -!- FUNCTION: Involved in the regulation of both adhesion and cell
CC morphology and cancer progression. Functions as an anti-adhesive
CC molecule that maintains an open filtration pathway between neighboring
CC foot processes in the podocyte by charge repulsion. Acts as a pro-
CC adhesive molecule, enhancing the adherence of cells to immobilized
CC ligands, increasing the rate of migration and cell-cell contacts in an
CC integrin-dependent manner. Induces the formation of apical actin-
CC dependent microvilli. Involved in the formation of a preapical plasma
CC membrane subdomain to set up initial epithelial polarization and the
CC apical lumen formation during renal tubulogenesis. Plays a role in
CC cancer development and aggressiveness by inducing cell migration and
CC invasion through its interaction with the actin-binding protein EZR.
CC Affects EZR-dependent signaling events, leading to increased activities
CC of the MAPK and PI3K pathways in cancer cells.
CC {ECO:0000269|PubMed:10982412}.
CC -!- SUBUNIT: Monomer; when associated with the membrane raft. Oligomer;
CC when integrated in the apical membrane. Interacts with SLC9A3R2.
CC Interacts (via the C-terminal PDZ-binding motif DTHL) with SLC9A3R1
CC (via the PDZ domains); the interaction take place early in the
CC secretory pathway and is necessary for its apical membrane sorting (By
CC similarity). Found in a complex with EZR, PODXL and SLC9A3R2.
CC Associates with the actin cytoskeleton through complex formation with
CC EZR and SLC9A3R2. Interacts (via the C-terminal PDZ-binding motif DTHL)
CC with SLC9A3R1 (via the PDZ domains); interaction is not detected in
CC glomerular epithelium cells. Interacts (via the C-terminal PDZ-binding
CC motif DTHL) with SLC9A3R2 (via the PDZ 1 domain); interaction is
CC detected in glomerular epithelium cells. Interacts with EZR.
CC {ECO:0000250, ECO:0000269|PubMed:11457882}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:11457882}. Cell projection, microvillus
CC {ECO:0000269|PubMed:11457882}. Membrane raft {ECO:0000250}. Cell
CC projection, lamellipodium {ECO:0000250}. Cell projection, filopodium
CC {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Membrane
CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
CC Note=In single attached epithelial cells is restricted to a preapical
CC pole on the free plasma membrane whereas other apical and basolateral
CC proteins are not yet polarized. Colocalizes with SLC9A3R2 at the apical
CC plasma membrane during epithelial polarization. Colocalizes with
CC SLC9A3R1 at the trans-Golgi network (transiently) and at the apical
CC plasma membrane. Its association with the membrane raft is transient.
CC Forms granular, punctuated pattern, forming patches, preferentially
CC adopting a polar distribution, located on the migrating poles of the
CC cell or forming clusters along the terminal ends of filipodia
CC establishing contact with the endothelial cells. Colocalizes with the
CC submembrane actin of lamellipodia, particularly associated with
CC ruffles. Colocalizes with vinculin at protrusions of cells. Colocalizes
CC with ITGB1. Colocalizes with actin filaments, EZR and SLC9A3R1 in a
CC punctate pattern at the apical cell surface where microvilli form (By
CC similarity). Colocalizes with EZR and SLC9A3R2 at the apical cell
CC membrane of glomerular epithelium cells. Colocalizes with PARD3, PRKCI,
CC EXOC5, OCLN, RAB11A and RAB8A in apical membrane initiation sites
CC (AMIS) during the generation of apical surface and luminogenesis (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Glomerular epithelium cell (podocyte) (at protein
CC level). {ECO:0000269|PubMed:11457882}.
CC -!- DOMAIN: Both the O-glycan-rich domain of the extracellular domain and
CC the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor
CC an apical sorting signal. The cytoplasmic domain is necessary for the
CC apical membrane targeting and renal tubulogenesis. The large highly
CC anionic extracellular domain allows to maintain open filtration
CC pathways between neighboring podocyte foot processes. The cytoplasmic
CC C-terminus PDZ-binding motif (DTHL) is essential for interaction with
CC SLC9A3R1 and for targeting SLC9A3R1 to the apical cell membrane. The
CC extracellular domain is necessary for microvillus formation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N- and O-linked glycosylated. Sialoglycoprotein (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the podocalyxin family. {ECO:0000305}.
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DR EMBL; AB020726; BAA78375.1; -; mRNA.
DR EMBL; AF109393; AAF14238.1; -; mRNA.
DR EMBL; BC070886; AAH70886.1; -; mRNA.
DR RefSeq; NP_620203.1; NM_138848.1.
DR RefSeq; XP_008760980.1; XM_008762758.2.
DR RefSeq; XP_017447916.1; XM_017592427.1.
DR AlphaFoldDB; Q9WTQ2; -.
DR CORUM; Q9WTQ2; -.
DR STRING; 10116.ENSRNOP00000016991; -.
DR GlyGen; Q9WTQ2; 7 sites.
DR iPTMnet; Q9WTQ2; -.
DR PhosphoSitePlus; Q9WTQ2; -.
DR jPOST; Q9WTQ2; -.
DR PaxDb; Q9WTQ2; -.
DR PRIDE; Q9WTQ2; -.
DR Ensembl; ENSRNOT00000077406; ENSRNOP00000075234; ENSRNOG00000012495.
DR GeneID; 192181; -.
DR KEGG; rno:192181; -.
DR UCSC; RGD:621878; rat.
DR CTD; 5420; -.
DR RGD; 621878; Podxl.
DR eggNOG; ENOG502S2JU; Eukaryota.
DR GeneTree; ENSGT00730000111314; -.
DR InParanoid; Q9WTQ2; -.
DR OMA; NWTKCEA; -.
DR OrthoDB; 1404598at2759; -.
DR PhylomeDB; Q9WTQ2; -.
DR TreeFam; TF333564; -.
DR PRO; PR:Q9WTQ2; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000012495; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; Q9WTQ2; baseline and differential.
DR Genevisible; Q9WTQ2; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:RGD.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0036057; C:slit diaphragm; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0072175; P:epithelial tube formation; ISS:UniProtKB.
DR GO; GO:0003094; P:glomerular filtration; IC:UniProtKB.
DR GO; GO:0050900; P:leukocyte migration; ISO:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:RGD.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0072015; P:podocyte development; IEP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0032534; P:regulation of microvillus assembly; ISS:UniProtKB.
DR InterPro; IPR013836; CD34/Podocalyxin.
DR InterPro; IPR017403; PODXL.
DR PANTHER; PTHR12067; PTHR12067; 1.
DR Pfam; PF06365; CD34_antigen; 1.
DR PIRSF; PIRSF038143; Podocalyxin-like_p1; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Cell projection; Glycoprotein; Membrane;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..485
FT /note="Podocalyxin"
FT /id="PRO_0000024757"
FT TOPO_DOM 25..386
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 408..485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 22..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 445
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0M4"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT MOD_RES 483
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00592"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 130
FT /note="T -> S (in Ref. 1; BAA78375)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="E -> G (in Ref. 1; BAA78375)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="N -> S (in Ref. 1; BAA78375)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 485 AA; 51658 MW; 54088032631C774E CRC64;
MRPTLALSAL LLLQLLLLST PSLSQDNGNK TDTSDITSID QNQDKPATNQ PSNATPKSSV
QPPTPTSIST SSPDPKATQS SNSSVTTTSD STTDRTSSST STVPTTSNSG QTVSSGGKSS
DKITTALPTT LGPVNASSQP TDLNTSTKLP STPTTNSTAS PHQPVSHSEG QHTTVQSSSA
SVSSSDNTTL LWILTTSKPT GTSEGTQPIA ISTPGITTPV STPLQPTGSP GGTESVPTTE
EFTHSTSSWT PVVSQGPSTP SSTWTSGSYK LKCDPAIKPH EELLILNLTR DSFCKGSPPN
ERFLELLCHS AKASFKPAED SCALELAPIL DNQAVAVKRI VIETKLSPKA VFELLKDKWD
DLTEAGVIDI HLGKEGPPEV NEDRFSLPLI ITIVCMASFL LLVAALYGCC HQRISQRKDQ
QRLTEELQTV ENGYHDNPTL EVMETPSEMQ EKKVVNLNGE LGDSWIVPLD NLTKEDLDEE
EDTHL
